Dr. Alka Kanaya is an Associate Professor in the Departments of Medicine, Epidemiology and Biostatistics at the University of California San Francisco. Trained in Internal Medicine and Epidemiology, over the past decade she has mentored several individuals at different levels in their training and developed a thriving program of multidisciplinary collaborative research focused on diabetes and cardiovascular disease epidemiology and prevention. Dr. Kanaya is at an ideal stage of her career for a K24 grant. Support from this award would allow her to leverage her research program to develop the careers of new patient-oriented researchers. She is currently funded by the NHLBI to conduct a prospective cohort study of South Asians called the MASALA study which is modeled on the existing Multi-Ethnic Study of Atherosclerosis (MESA) to understand the antecedents of diabetes and cardiovascular disease in this high risk ethnic group. With the support of the K24, Dr. Kanaya will extend the research program by adding measurements of ectopic fat and adipokines to the MASALA study cohort and make comparisons to four other U.S. ethnic groups in MESA. The Overall Aims of this K24 proposal are: (1) To measure ectopic fat depots and adipokines among 900 South Asians in the MASALA study and to describe and compare ectopic fat depots and adipokines between the South Asians and the four MESA ethnic groups after adjusting for age and overall body size. (2) To test the hypothesis that higher ectopic fat will be associated with worsened glucose tolerance; that adipokines will explain the association between the ectopic fat depots and glucose tolerance status; and that the increased prevalence of diabetes among the South Asians compared to the MESA ethnic groups will be explained by the ectopic fat depot and adipokines. (3) To test the hypothesis that higher amounts of ectopic fat will be associated with greater subclinical atherosclerosis; that adipokines will explain the association between the ectopic fat depots and subclinical atherosclerosis; and that the difference in subclinical atherosclerosis prevalence among the South Asians compared to the MESA ethnic groups can be explained by the ectopic fat depot and adipokines. (4) To determine whether baseline levels of ectopic fat are independently associated with incident cardiovascular events among South Asians after adjusting for traditional cardiovascular risk factors; and whether differences in CVD outcomes between South Asians and the MESA ethnic groups can be explained by the ectopic fat depot and adipokine levels. The K24 would insure sufficient time to pursue this natural progression of Dr. Kanaya's research while protecting time to devote to mentoring future clinical investigators in patient-oriented research. The plans for development, research, and mentoring were designed to complement each other and to create a synergistic effect of mentoring and research in patient-oriented research. The proposed mentoring, research, and career development activities actively leverage existing infrastructure, resources, and training initiatives provided by NIH, including Dr. Kanaya's active research program and the Clinical and Translational Science Institute (CTSI) at UCSF.